The purpose of this investigation was to define T lymphocyte phenotypes and immunoregulatory function in the intestine of patients with Crohn's disease. Crohn's disease and control patients undergoing surgical resection were studied. Intestinal lymphocytes were isolated by enzymatic digestion and compared to periferal blood lymphocytes. T lymphocyte phenotypes were determined using monoclonal antibodies and flow cytometry. Helper and suppressor T cell function were studied by addition of patient lymphocytes to co-cultures containing normal lymphocytes and pokeweed mitogen. Supernatant immunoglobulin was measured by RIA. The results of flow cytometry studies indicated that both Crohn's and control patients had a diminished proportion of Leu 3+ cells and a normal proportion of Leu 2+ lymphocytes in the intestine, compared to peripheral blood. Lymphocytes from both Crohn's and control patients were similar to autologous peripheral blood T lymphocytes in their capacity to provide help. Neither Crohn's nor control intestinal T lymphocytes suppressed immunoglobulin synthesis unless they were pre-activated with Con A or enriched for OKT8+ suppressor cells. In summary, first, normal intestinal lymphocytes are heterogenous with regard to T cell phenotypes and helper and suppressor T cell function; the predominant immunoregulatory effect of normal intestinal lymphocytes is to provide help under the conditions employed. Secondly, in contrast to patients with mild or inactive Crohn's disease, intestinal and peripheral blood lymphocytes of patients with moderate to severe activity of Crohn's disease have T lymphocyte phenotypes and immunoregulatory function which are similar to that of control lymphocytes. These findings may indicate that active intestinal inflammation in Crohn's disease may in part be due to inadequate recruitment or activation of suppressor cells in the intestine.